tylosis palmaris et plantaris familiaris associated - SAMJ Archive ...

170 S.A. MEDICAL JOURNAL 4 March 1961 

finns and very soon the new drug is advertised under 

many different proprietary names. Alternatively, a series 

of compounds may be introduced with very similar 

therapeutic actions, but differing only lightly in their 

chemical constitution. These all become advertised under 

different names. The result is confusion in the nomenclature 

of new drugs. After an interval a new drug may be 

accepted for the phannacopoeia, and is given an official 

name. For obvious reasons it becomes difficult to establish 

the popular use of the official name. 

Practitioners are well aware of the confusing nomenclature, 

and pharmacists are al 0 perplexed by the multiplicity 

of similar-sounding names. There are many 

examples that could be quoted but a few will suffice. 

Among the tranquillizers there are triflupromazine and 

trifluoperazine, perphenazine and prochlorperazine. There 

are digoxin and digitoxin; raudixin and redoxon; sigmagen 

and sigmamycin; romical and romilar; librium and 

libratar; and m'etreton and meticorten. There must be even 

better examples of drugs with different actions and indications 

whose names are very similar. It is surprising that 

accidents do not occur frequently from the use of the 

wrong drug. It is to the credit of doctors, nurses, and 

phannacists that mistakes occur very infrequently. 

It would be a blessing to both prescribers and dispensers 

of drugs if the manufacturers would relegate their brand 

names to second place and market their products as 

penicillin (Smith) or penicillin (Jones). Unfortunately this 

method of nomenclature is unacceptable to commercial 

finns, although it is applied to insulin preparations. . 

As the output of new preparations increases, the search 

for new names becomes a big problem. One firm in the 

USA has 'commissioned a machine to produce a dictionary 

of forty-two thousand nonsense words of an appropriate 

scientific look and sound'. An official said 'Thinking up 

names has been driving us cuckoo ... A good trade 

name carries a lot of weight with doctors ... there are 

enough names in the new dictionary to keep us going 

for years ... We don't yet know what proportion of 

names is unpronounceable ... how many are obscene ... 

how many objectionable on other grounds of good taste. 

"Godamycin" would be a mild example1.' 

It is therefore clear that a difficult situation confronts 

the practising physician. Perhaps the doctors have themselves 

to blame for this. In many countries attempts have 

been made and progress achieved in obtaining uniformity 

on a national level. The World Health Organization has 

attempted to coordinate these efforts at an international 

level, and has published lists of proposed international 

non-proprietary names for drugs. 

It is obvious that there is much to be done, and a 

difficult task lies ahead to avoid the confusion which 

exists in the multiplicity of names for the same preparations 

and the similarity of names for different preparations. 

1. New Yorker. 14 Juh' 1956. 

TYLOSIS PALMARIS ET PLANTARIS FAMILIARIS ASSOCIATED 

~TH CLINODACTYLY 

- 

GORDO. K. KLINIWORTH, B.sc., M.B., B.ar. (RAND) and INGRAM F. ANDERSON, M.B., B.CH. (RAND) 

Department of Medicine, Johannesburg General Hospital 

Tylosis palmaris et plantaris familiaris (hereafter referred 

to as tylosis) is a familial ectodermal anomaly of the 

palms and soles producing marked hyperkeratosis. It is 

to Thost 25 and Unna 27 that credit must be given for the 

original description of the disease. Since then numerous 

reports have appeared in the literature. The most comprehensive 

review of the whole subject, however, is that 

of Cockayne. 3 Several workers have noted the rare association 

between tylosis and other conditions. Among them 

are Howel-Evans et aP who discussed the association of 

thi disease with carcinoma of the oesophagus. Modern 

genetic studies have focussed attention on the co-existence 

of familial conditions. In view of this it was felt necessary 

to study, in more detail, the family of a patient who 

presented with a myocardial infarction and a family history 

of tylosis. 

A family of 59 members through 5 generations was 

investigated. wherever possible they were personally interviewed. 

Where this was not practicable a first-hand collaborative 

history was taken from several other family members. 

Particular attention was paid to the presence of 

tylosis and other ectodermal anomalies, arterial degenerative 

disorders, dysphagia, and other abnormalities. In 

those deceased the cause of death was ascertained. 

CASE REPORT 

Mr. C.P., aged 42 years, lorry driver, ""as admitted to the 

Johannesburg General Hospital on 12 September 1959 with a 

myocardial infarction following a period of angina of effort. 

Typical hyperkeratotic lesions of the soles and palms, with 

extension of the lesion to the dorsal surfaces of the index 

and little fingers, were present. Similar small areas of horny 

thickening of the skin were noted over the extensor aspects 

of both elbows, overlying the tendo Achillis, and to a lesser 

extent in the dorsal ankle crease. An interesting feature was 

anhydrosis of the affected areas. The patient gave a good 

description of tylosis in other members of his family. The 

condition apparently became evident when he began to crawl 

at the age of 6 months but had not really troubled him 

until he became engaged in manual labour. He noted that his 

skin was much improved in a humid atmosphere and that use

4 Maart 1961 S.A. TYDSKRIF VIR GENEESKUNDE 171 

ill 

IT I 

•• 

UAMW£O 

[J et 

0 0 

NOT 

TYlOSlS AND CUHOOACTYU , 

rn 

OA1IW«O 

CD 

[XAIIIIfWEO NO HtSTOflV OF f)TH(A CONOITlC»i 

IJ ~ 

" 

,. 

1 

IJ () 

(llAMlN(O fYlOSlS OJrf\.y 

NO T'f't..OSIS _0 CUHOO ...cn , 

6000 ~1()lt' or mosrs Iro() loIrSTOIll' 01' Cl.JNOOACTTlY 

Fig. 1. Family tree of patient, showing 4 generations (1, 11, ill and IV) md one member in fifth generation. Arrow 'points to patient (Ill 12). 

TABLE I. SUBJECTS WHO WERE PERSONALLY EXAMINED OR HAD HISTORY OF TYLOSIS 

"!- 

Distribution and severity oflesions 

.. ~ 

-c ... 

Ol 

:: 

 

'c- 

'o-~ 

"".::; 

~ 0"" 

E I 

~ "'"13 .. .. - too- 

0 .. .::; 

~ .~ 

'" 

§ .;:: ~ 

~ too'"' ~.::; -'- 

~ :=~ .so c::-§ 

-~ 

... '" '"' ~6 ~:::: "13~ ~ 

)( g:, .~ a ~ ..::: ~- ~~ 

:::~ 

.. 

~..s: 

O-c 00 

.. c:: ,. - 

-~ 

t':l ~ ~ ~~ ~~ ~ ~ l::l"Ol ~~ l::l~ ~~ v)..:;:: 

~ 

~ 

~~ 

I 4 F 95 NE i> Yes 

IT 2 F 50 E L Yes ++ ++ + Increased 

IT 3 F 51 NE D Yes 

IT 5 F 64 E L Yes +++ +++ + + Decreased 

ill 4 M 50 E L No Yes ormdl 

ill 5 F 11 E L No No Normal 

ill 6 F 9 E L No 0 Normal 

ill 7 M 7 E L No No Normal 

ill 8 F 38 E L Yes ++ +++ + + Yes Decreased 

ill 10 F 33 E L No 0 Normal 

ill 12 M 42 E L Yes +++ +++ + + No Decreased 

ill 13 M 35 E L Yes ++ +++ + No Decreased 

ill 14 F 24 E L No Yes Normal 




IV 5 F 17 NE L Yes 

IV 7 F 14 E L Yes ++ ++ + + Yes Decreased 

IV 8 M 13 E L No 0 ormal 

IV 9 F 7 E L No 0 ormal 

IV 10 F 14 E L No 0 ormal 

IV 11 M 12 E L 0 0 ormal 

IV 12 F 10 E L 0 Yes ormal 

IV 16 M 5 E L Yes ' '..J... 

+++ TT, + + Yes Decreased 

IV 17 F 12 E L Yes ++ ++ Yes ormal 

IV 18 M 10 E L Yes ++ ++ + + + Yes Decreased 

IV 19 M 7 E L Yes ++ ++ + + ormaJ 

IV 20 F 3 E L Yes ++ ++ 0 ormal 



IV 24 F 5 E L 0 Yes ormal 


IV 26 F 6 E L 0 0 ormaJ 



F=female, M=male, NE=not elGUIlined, E=examined, D=deceased, L=living, + = slight, ++= more pronounced, and +++-severe. 

t For numbers refer to Fig. 1.


of the hands, especially in cold dry weather, resulted in gm s 

thickening, cracking and even bleeding of the palmar skin. 

Except for the presence of tylosis and evidence of acute myocardial 

infarction, 

essentially normal. 

general examination of the patient was 

Family 

[n the 59 member of the family there were at least 14 with 

tylosis (9 female, 5 male). Of the 32 member per onally 

examined, 11 were affected; a good de cription was obtained 

regarding 3 other (Fig. 1 and Table D. In all affected ca es 

the age of on et was in the fir t year of life. In 10 of the 

ubjects clinodactyly was noted. In this condition the little 

finger is curved inwards towards the other fingers. No other 

abnormality of skin or skeleton was noted nor were there 

any abnormalitie of hair or teeth. Besides the patient, 2 (1I5, 

llIJ I) of the 33 living member bad sustained myocardial 

infarctions. 0 other members gave a history of cardiovascular 

disease. There wa no history of dysphagia or buccal leukoplakia 

and as far as could be ascertained no one had died of 

oe ophageal carcinoma. Of the 7 in whom the cause of death 

was known (14, Ill, 113, 1I4, ITI9, III18, and IIJI9), 3 were 

due to cardiac di ease (14, Ill, and 113). one of the 7 bad 

died of malignant disea e. 

DISCUSSION 

Tylosis 

Much confusion exists in the literature regarding the 

terminology of the group of hyperkeratoses. Tylosis palmaris 

et plantaris has the following synonyms: '3 keratosis 

palmaris et plantaris, hyperkeratosis palmaris et plantaris, 

ichthyosis palmaris et plantaris, keratoderma palmare et 

plantare, and symmetrical keratoderma. 

The condition has been described as rare.:!:! In Nprthern 

Ireland the incidence was calculated to be I in 40,000. 2 ' 

Histopathologically,IO the skin usually shows considerable 

hypertrophy of all its layers, more espe ially the stratum 

corneum, which is grossly thickened. The tratum granulosum 

is normal in appearance and there is no change in 

the stratum spinosum. Occasionally there i flattening of 

the papillary body. These papillae may be increa ed fivefold 

in depth. The dermis is unaffected, except outside the 

area of horny thickening or, where fissures are present, 

when mild inflammatory changes may be noted. The sweat 

glands and their ducts may be hypertrophied. The histopathological 

section in the present case i shown (Fig. 2) 

compared with a normal section (Fig. 3). 

Clinically tylosis is rarely manifest at birth and is usually 

not recognized until the third or fourth month. In exceptional 

case the onset may be delayed until the age of 

6 years. I9 . 23 The lesions are bilateral, symmetrical, and 

situated almost exclusively on the palms and soles (Figs. 

4 and 5) either of which may be predominantly involved. 

Occasionally the hyperkeratosis is noted on the dorsum 

of the hands, feet and phalanges. In some cases it is present 

on ·the extensor surfaces of the elbows, over the knees 

and about the ankles. I5 . I9 The nails may be involved and 

become thickened and opaque and are raised up from 

the nail bed by a horny accumulation beneath them. This 

complication may result in more severe symptoms than 

those produced by the skin lesions. 

The distribution is determined to a large extent by 

physical factors such as pressure and friction. Thus, in 

infants, the lesions will be on the knees; on beginning 

to walk the feet are most involved in the weight-bearing 

areas of the soles; the manual labourer exhibits gross 

Fig. 2. Low-power section of hyperkeratotic palmar skin 

(x 45). 

Fig. 3. Low-power section of normal palmar skin (x 45).


Fig. 4. This shows the bilateral lesions of tylosis on the 

palms. 

lesions of the palms, and the office worker may have a 

predominant affection of the elbows. 

The condition varies not only in intensity in different 

individuals of the same family but also at different times 

in an affected individual. The condition is aggravated 

during very warm or very cold weather and also during 

manual labour, especially if the work involves exposure 

of the hands to moisture and cold." The influence of 

climatic and occupational factors was also well illustrated 

in members of the family we studied. 

Many subjects may be so slightly affected that they do 

not realize that they have the condition until their attention 

i drawn to it. On the other hand, marked thick~ning 

of the palmar skin may reduce tactile sensibility and 

Fig. 5. This shows the bilateral lesions of tylosis OD the 

soles. Note symmetry of the lesions. 

interfere \ it.h the finer finger mo emenl . P in i nOl 

u ually a marked fearure of the h nd I ion. although 

Ander on l reponed a ca e with e tremely painful I ion 

of the hand. The ole tend to be more painful than the 

palm and thi may interfere with normal walking. ffe ted 

area are predi po ed to fi uring b au e of a la k of 

normal ela ticity.2:!·~ The normal fi ure are ex gger ted 

and produce a mo aic-like appearance. lnvol emenl of the 

dermis by the fi ures cau e pain and ometime h e 

morrhage. 

Hyperhydro i i pre ent in the majorit of ca reponed 

in the literature. Familie are on rerord in whi h 

sweating was dimini hed. 3 In the famil under on ideration 

both states obtained. There appeared to be an in erse 

relationship between the degree of hyperkerato i and the 

amount of sweating, and we ugge t that the hypohydro i 

in severely affected cases may be due to ob tru tion of 

the sweat-gland duct by the thickened and hyperkeratotic 

skin. Sweat-gland hypertrophy i not an uncommon feature 

and may account for the increa ed weating noted in 

milder cases. 

Tylosis should be differentiated from the acquired type 

of hyperkeratosis, notably lichen simplex (neurodermatili ), 

contact dermatitis, psoriasis, tertiary yphili, fungal infeclions 

(particularly TrichophYTOn rubrum), volar verrucae. 

calluses, and the now rarely- een ar enical keratoderma. 

19 • 23 • 2S 

Certain familial skin conditions resembling tylo i mu t 

be differentiated. Hereditary di eminate keratoderma 

palmaris et plantaris consists of multiple, ymmetrical. 

discrete plaques on the palms and soles. The lesions do 

not coalesce and the onset usually occurs at adole ence 

but is sometimes delayed until adulthood. 21 

Mal de Meleda 3 is a rare type of palmar and plantar 

hyperkeratosis described only on the i land of 1eleda off 

the Dalmatian coa t. Mo t of the i-nhabitan are onsanguinously 

related; this favour tran mi ion of lhe 

di ease by what icon idered to be .a rece ive gene. In 

addition to the usual site the hyperkeratosi involve 

the dorsum of the hands and feet, and may extend up 

the legs and forearms to the elbow and knees. Hyperhydrosis 

is present. 

There is no known cure for tylosis. Amelioration may 

occur with change of occupation or during humid weather. 

Treatment is purely palliative and numerou therapeutic 

mea ures have been employed with variable temporary 

benefit. Keratolytics uch a alicylic-acid preparation 

are employed to soften and remove the homy layer. 

Superficial X-ray therapy ha been advo ated by ome 

but has not met with general approval, mainly becau e 

of the risk of causing carcinoma and becau e effective 

do age may lead to cicatricial atrophy with teJangiecta i .10 

Various hormone, notably thyroid extract and oe trogen , 

have been tried. The u e of large dose of vitamin A ha 

been reported to control the gro s manife tation of the 

disease. 16 Its use is purely empirical and no ati factory 

explanation of the mechanism is forthcoming. andpapering 

and mechanical abra ion of the affecled area ha been 

used. 10 severe ca e benefit ha been claimed by complete 

exci ion and grafting.'·13·l:l·29 

Tylosis and Associated AbnormaliTies 

Many abnormalitie as ociated with tylo i have been


Fig. 6. Tylosis and clinodactyly. Note radial deflection of both little fingers. 

Fig. 7. Clinodactyly. X-ray showing sloping of the distal surface of the middle 

shortening of the radial surface of the phalanx. 

fingers. The rest of the phalanges are normal. The incidence 

has been calculated at 1 in 1,000 in Northern Ohio. s Hersh 

et af.S fed that the term clinodactyly should be limited to 

those cases which are due to incomplete ossification and 

should not be confused with other causes of familial 

crooked little fingers such as those due to abnormal tendons5-7 

and to fused ossification,u 

Genetic Transmission 

Tylosis is inherited as a Mendelian dominant with high 

penetrance. It appears to be controlled by a single autosomal 

gene. Cockayne 3 reviewed 47 families in the literature 

and the proportion of affected to normal members 

was 594: 483. The sex ratio was 318 males to 284 females. 

He reported 2 small families in whom the lesion only 

occurred in the females and not in the males. Subsequent 

studies, however, indicated that the two sexes are equally 

affected and no race is immune. 20 • 23 

Lawler and RenwickJ..i are of the opinion that there are 

at least 2 types of inherited tylosis which apparently run 

true in families and appear to be due to different genes. 

The 2 forms have been differentiated on clinical grounds. 

Type A has a variable age of onset ranging from 5 to 15 

years, whereas Type B is recognizable during the first year 

of life. The latter is clinically distinguishable from Type A 

by the uniform thickness of the keratosis, by the sharply 

delimited edges of the lesion, and by the rare incidence 

of painful fissuring. Both types are inherited as a 

Mendelian dominant. This clear-cut distinction was not a 

feature of our cases, since fissuring was not an uncommon 

finding in lesions which had been noted in the first 

year of life with relatively sharply demarcated edges and 

in which keratosis was of uniform thickness. 

Tylosis is due to a mutant gene and the extent, distribution 

and severity are independent aspects which are 

largely determined by composite genetic and environmental 

factors. Thus the same mutant gene may cause several 

distinct clinicopathological pictures and this difference in 

expressivity may be evoked to explain the large and varied 

nomenclature applied to the hyperkeratoses. 

Clinodactyly has not previously been described.' asso- 

described in isolated instances. Howel-Evans et al. 9 reported 

the association of carcinoma of the oesophagus 

and tylosis in 2 families. There was unequivocal evidence 

that carcinoma of the oesophagus was associated with 

tylosis in 17 of their cases, and in only 1 case in which 

the neoplasm was found was it impossible to establish 

that tylosis was present. Members of the family unaffected 

by tylosis were unaffected by carcinoma. In the cases 

of carcinoma of the oesophagus in which the oesophageal 

epithelium adjacent to the tumour was examined histologically, 

no evidence of hyperkeratosis was found. The 

association between palmar and plantar hyperkeratosis and 

leukoplakia of the mouth has been recorded. 12 • 23 • 26 

Malignant degeneration in areas of hyperkeratosis has been 

considered likely by some dermatologists,IS and Ingram and 

Brain lO mentioned a case in which squamous carcinoma 

developed in tylosis. 

Hanhart (quoted by Cockayne 3 ) described a Swiss family 

in which the affected members developed tylosis and 

multiple lipomata during late adolescence. Cockayne 3 commented 

that the late age of appearance of tylosis made 

it doubtful whether it was the ordinary form of the 

disease. 

Tylosis has been reported to occur occasionally with 

extensive ichthyosis hystrix or with epidermolysis bullosa. IO 

It has been found associated with other ectodermal abnormalities 

3 IO • ,23 or with hypogenitalism, oxycephaly, clubbing 

of the fingers, or mental retardation. 2 • 3 

Clinodactyly, as described in our cases, is a shortening 

of the middle phalanx of the fifth finger, mainly on its 

radial aspect, which results in a radial deflection of the 

terminal phalanx of from 15° to 30° (Fig. 6). The remaining 

digits are normal and there is no flexion curvature. s On 

X-ray (Fig. 7), the middle phalanx of the little finger is 

slightly shorter on the radial side, thus forming an appreciable 

slope on its distal surface. X-ray observations indicate 

that this seems to be caused by a slowing-down process 

of ossification, specifically at the upper radial part of the 

middle phalanx of the fifth finger. Due to this slanting, 

the distal phalanx is inclined inwards towards the other 

phalanx of the little finger due to


ciated with tylosis. The only reported association of clinodactyly 

is that with webbing of the toes. s In the family 

we studied there were 10 members with clinodactyly 

6 female and 4 male. In 8 cases the curving of the little 

finger was bilateral but in 2 this curving was only present 

in the left hand. Of those with clinodactyly, 6 were 

affected with tylosis as well. Clinodactyly is transmitted 

as an autosomal dominant. Lack of complete penetrance. 

was shown by the fact that in 6 cases the parents did not 

have the condition. In 1 case (N24) neither the parents 

nor the grandparents had clinodactyly. These features of 

dominant transmission with incomplete penetrance have 

been reported by others. s 

Is there a genetic linkage between clinodactyly and 

tylosis, or is the association purely one of chance? We 

were unable to obtain statistically significant results in 

favour of genetic linkage, using the sibling pair method 

of PenroseY·lS However, assuming that the incidence of 

tylosis and clinodactyly in South Africa is 1 in 40,()()()24 

and 1 in I,OOOS respectively, the probability of these 2 

co~Oitions occurring together is in the region of 1 in 40 

miJ1fon. 

SUMMARY 

In a family affected with tylosis palmaris et plantaris 59 

members were studied. The family tree and the mode' of 

genetic transmission are outlined. The incidence, histopathology, 

clinical features, differential diagnosis and treatment 

of tylosis are discussed. The association of tylosis 

and clinodactyly is noted. In addition some of the reported 

abnormalities occurring with tylosis are revi"ewed. 

We wish to thank Profs. G. A. Elliott, B. J. P. Becker, and 

P. V. Tobias for encouragement and a i lance in the preparation 

of this article; the Photographic Unit of the Department 

of Medicine and Mr. S. Dry of the Anatomy Department, 

Univer ity of the Witwater rand, for reproduction of 

the figures; and Dr. K. F. Mills, Superintendent, Johanneburg 

General Hospital, for perrni sion to publish. 

REFERE CES 

1. Anderson, J. (1951): Brit. J. Deem., 63, 127. 

2. Bureau, G., Horeau, M., Barriere, H. and DuFage, C. (1958): Bull. 

Soc. rran9. Derm. Syph., 65, 32 . 

3. Cockayne, E. A. (1933): The Inherited Abnormaliries of the Skin and 

itS Appendages. London: Oxford University Press. 

4. Dencer, D. (1953): Brit. Plast. Surg., 6, 130. 

5. Heffner, R. A. (1924): J. Hered., IS, 323. 

6. Idem (1929): Ibid., 20, 395. 

7. Idem (1941): Ibid., 32, 37. 

8. Hersh, A. H., De Marinis, F. snd Stecher, R. M. (1953): Amer. J. 

Hum. Genet., 5, 257. 

9. Howel-Evans, W., McConnell, R. B., Clarke, C. A. and Sheppard, P. M. 

(1958): Quart. J. Med., 27, 413. 

10. Ingram, J. T. and Brain, R. T. (1957): Sequeira's Diseases of rhe Skin, 

6th ed. London: Churchill. 

11. Knenner, D. M. (1934): J. Hered.. 25. 329. 

J2. Kumer, L. and Loos, H. O. (1935): Wien. kJin. Wschr., 48, 174. 

13. Landazuri, H. F. (195 ): Plast. Reconstr. Susg., 22, 557. 

14. Lawler, S. D. and Renwick, J. H. (1957): Personal communication to 

Howel·Evans et al. loco cil.9 

15. Ormshy, O. J. and Montgomery, H. (1948): Diseases of rhe Skin, 

7th ed. Philadelphia: Lea and Febiger. 

16. Porter, A. D. (1951): Brit. J. Derm., 63, 123. 

17. Penrose, L. S. (1935): Ann. Eugen., 6, 133. 

18. Idem (1938): Ibid., 8, 233. 

19. Pupa, J. A. and Farina, R. (1953): Plast. Reconstr. Surg., 12, 446. 

20. SeOlt, O. L. S. In Sorsby, A. ed. (1953): Clinical Genetics. u.ndon: 

Buttesworth. 

21. SeOlt, M. J., Costello, M. J. and Simuangco, S. (1951): Arch. Derm. 

Syph., 64, 301. 

22. Semon, H. C. G. (1953): An Atlas of rhe Commoner Skin Diseases, 

4th ed. Baltimore: Williams and Wilkin.

tylosis palmaris et plantaris familiaris associated - SAMJ Archive ...

Create successful ePaper yourself

Delete template?

Save as template?